Department of Pediatrics, University Medical Center Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
Department of Ophthalmology, Experimental Ophthalmology, University Medical Center Eppendorf, Martinistr. 52, 20246, Hamburg, Germany.
CNS Drugs. 2019 Apr;33(4):315-325. doi: 10.1007/s40263-019-00620-8.
The neuronal ceroid lipofuscinoses comprise a group of neurodegenerative lysosomal storage disorders caused by mutations in at least 13 different genes and primarily affect the brain and the retina of children or young adults. The disorders are characterized by progressive neurological deterioration with dementia, epilepsy, loss of vision, motor disturbances, and early death. While various therapeutic strategies are currently being explored as treatment options for these fatal disorders, there is presently only one clinically approved drug that has been shown to effectively attenuate the progression of a specific form of neuronal ceroid lipofuscinosis, CLN2 disease (cerliponase alfa, a lysosomal enzyme infused into the brain ventricles of patients with CLN2 disease). Therapeutic approaches for the treatment of other forms of neuronal ceroid lipofuscinosis include the administration of immunosuppressive agents to antagonize neuroinflammation associated with neurodegeneration, the use of various small molecules, stem cell therapy, and gene therapy. An important aspect of future work aimed at developing therapies for neuronal ceroid lipofuscinoses is the need for treatments that effectively attenuate neurodegeneration in both the brain and the retina.
神经元蜡样脂褐质沉积症包括一组神经退行性溶酶体贮积症，由至少 13 种不同基因突变引起，主要影响儿童或青年的大脑和视网膜。这些疾病的特征是进行性神经恶化，伴有痴呆、癫痫、视力丧失、运动障碍和早逝。虽然目前正在探索各种治疗策略作为这些致命疾病的治疗选择，但目前只有一种经临床批准的药物被证明可有效减缓特定形式的神经元蜡样脂褐质沉积症（CLN2 病）的进展，即 cerliponase alfa（一种溶酶体酶，注入 CLN2 病患者的脑室）。治疗其他形式的神经元蜡样脂褐质沉积症的方法包括使用免疫抑制剂来拮抗与神经退行性变相关的神经炎症、使用各种小分子、干细胞疗法和基因疗法。未来旨在开发神经元蜡样脂褐质沉积症治疗方法的一个重要方面是需要能够有效减缓大脑和视网膜中神经退行性变的治疗方法。
